Maturity onset diabetes of the young. Is it in the gene?

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Infections occur due to different reasons. Some of them occur due to infections while others arise among family members in various generations due to genetically problems. There is a question as to whether Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that occurs at adolescence or early in adulthood. MODY accounts for a low percentage of diabetes cases but is still a cause of worry. For example, up to 2% of 20 years or younger in the United States have MODY.

Researchers have found out that gene mutations are a cause of MODY thus it is in the gene. The gene mutations affect the pancreas interfering with its ability to produce insulin. It then leads to high levels of blood glucose and with time it may damage the body tissues. High blood glucose levels usually harm tissues in the blood vessels, eyes, nerves and kidneys .clinical features of MODY will depend on gene mutations affecting a person.

Genes provide instructions within the cell on how to make proteins. The protein will malfunction if a gene undergoes change or mutation. Genetic mutations that cause diabetes affect the proteins that give the body an ability to produce insulin or the ability of insulin to reduce the blood glucose. A person has two copies for most genes after inheritance of one gene for each from both the father and mother.

Young people with some types of mutations might have a slightly higher level of blood sugars that stay stable throughout the life. They can have mild symptoms of diabetes or none but might not develop any long-term complications. It is only during a routine blood test that there will be the discovery of high blood glucose levels. Nonetheless, other forms of mutation require specific treatment with a type of oral diabetes medicine called sulfonylureas or insulin.

Usually, there is a confusion between MODY and diabetes type 1 and 2.

These are the most common types of diabetes and polygenic meaning that they have a relationship to defect or a change in the multiple genes. Environmental factors such as obesity for type 2 diabetes are also a contributor to the development of polygenic types of diabetes. These are the forms of diabetes that run in the family. Doctors diagnose polygenic types of diabetes by testing the blood sugar also known as blood glucose in individuals who show symptoms or risk factors for diabetes.

In the past, most people with MODY did not become overweight or obese. They also did not have other risk factors that occur during type 2 diabetes. This can be abnormal blood fat or high blood pressure levels. However, more people with MODY are showing signs of becoming overweight not because of diabetes but the general way of life where more people, especially in developed countries, are becoming obese.

Although MODY and type2 diabetes may run in families, those with the latter will have a family history of diabetes in successive generations. It means that MODY in a child is a manifestation of a similar condition in a parent and grandparent.

Genetic Heterogeneity of MODY and causes

Heterogeneity means the diversity in character or content. Due to genetically diversity MODY are in the following types:

MODY1: Occurs due to the heterozygous mutation in hepatocyte nuclear factor -4-alpha gene (HNF4A) on chromosome 20.

MODY2: The cause is a heterozygous mutation in glucokisanegene (GCK) on chromosome 7.

MODY3: MODY 3 occur due to a heterozygous mutation in hepatocyte nuclear factor alpha gene (HNF1A) on chromosome 12q24.2.

MODY 4: The cause is a heterozygous mutation in the pancreas/duodenum homeobox protein one gene, PDX1 on chromosome 13q12.1.

MODY5: Heterozygous mutation in a gene encoding hepatic transcription factor-2, TCF2 on chromosome 17cen-q21.3. Is the cause of MODY 5?

MODY 6: Heterozygous mutation in NEUROD1 gene on chromosome 2q32

MODY7: Heterozygous mutation inKLF11gene on chromosome2q32.

MODY8: MODY 8 also called diabetes pancreatic exocrine dysfunction syndrome occurs due to heterozygous mutation I CEL gene on the chromosome 9q34.

MODY9: Happens after a heterozygous mutation on the PAX4 gene on the chromosome 7q32.

MODY10: Occurs due to a heterozygous mutation in insulin gene (INS) on chromosome 11p15.5.

MODY11: Heterozygous mutation in BLK gene 191305 on chromosome 8p23.

MODY13: Heterozygous mutation inKCNJ11 gene on chromosome11p15.

MODY14: Heterozygous mutation inAPPL1 gene on chromosome 3p14.

Common genes that cause the occurrence of MODY

Most maturity onset diabetes of the young cases occurs due to these causes.

HNF1-alpha-This gene is the cause of around 70 % of diabetes by reducing the amount insulin the pancreas should make. HNF1-alpha usually causes the development of diabetes in adolescence or the early twenties, and people it affects do not need to take insulin as part of their treatment. Group tablets in small doses called sulphonylureas can treat it in the same way it doctors use it for treatment of Type 2 diabetes.

HNF1-beta-this type of MODY makes people get variety o health problems including uterine abnormalities, gout, and renal cysts in the kidneys alongside diabetes. The renal cysts often can occur in the womb before childbirth, but diabetes develops later and receptive to insulin treatment together with eating a healthy diet and regular physical exercises. The complications of diabetes can resemble those of HNF4-beta MODY.

HNF4-Alpha: This cause of MODY does not frequently occur like others, but it is likely to occur among the people who inherited a change in this gene are likely to have been born with a birth weight of 4 or kilos (nine pounds). The patient might have a history of low blood sugar at birth or soon after and might need treatment. The people with HNF4-alpha require therapy with a tablet that might require progress to use of insulin.

Glucokinase-glucokinase is a gene that helps the body in recognizing the level of blood glucose in the body. If this gene fails to work correctly, the body allows the level of blood glucose to increase and become higher than the average level. Blood glucose levels among the people with glucokinase MODY are slightly higher than usual amount which is between 5.5 to 8mmol/l.

This type of MODY does not cause visible symptoms hence a doctor can only pick its existence through routine testing such as during pregnancy. MODY from glucokinase unlike other type does not long-term complications hence patients can manage it without any medical treatment. Physical activity and eating a healthy balanced diet helps to maintain the right levels of blood glucose and cholesterol which in turn decrease the risk of complications.

Study outcomes on Population genetics of Maturity-onset diabetes of the young

For many years, people associated onset of diabetes to age. Studies on MODY are not old as about the other types of diabetes, but there are still findings on research many years ago. The researchers were aiming to determine what it was, likely causes and the population where it was possible to occur. MODY is more prevalent in specific regions than others. Studies at various places and years by these researchers brought out these findings of MODY.

1979: Rimoin stated that it affects more people in Romania than at other places.

1987: Winter and other researchers out MODY in America was more common in the Black populations .they found a typical form in 12 out of 129 patients and in the last two generations of nine in 12 families in the probands. The study scope was on 12 probands and 14 of the diabetic relatives. There were no findings of cells in Islet cell auto antibodies, and thyroid microsomal auto antibodies were present in only one. The study did not have an increase in frequencies of insulin-dependent diabetes relating antigen HLA-DR3 and DR4 among the probands and diabetes did not co-segregate with HLA haplotypes in informative families.

1995: A study by Leadermann stated that MODY occurrence is about 5% among patients with type 2 diabetes in most populations.

2001: Fajans states that members of families with a clinical history that resembles diagnosis of MODY but did not have mutations in any of the MODY-relating genes makes up 15-20 per cent of the Europeans with clinical MODY. The percentage reaches the highest percentage in Japan where researchers say it goes up to 80%.

MODY2 and MODY3 are the two most prevalent forms of diabetes in the young. They account for more that 80% of the MODY patients in Caucasians. Mutations in the HNF4A gene are not common, and even research on the Japanese populations where MODY is highly prevalent found that it affects only one out of 57 patients.

Other subtypes are rare disorders that only a few families report. According to the outcome of findings by Yamada et al. (2000) suggested that there is an explanation by known MODY genes about the existence of diabetes in 80% of MODY patients.

Studies on 146 families in a condition that fulfils the minimum criteria for MODY 2 had at least one member diagnosed for with the disease before age 25. Thirteen of the families had MODY3 mutations while mutations for two others were MODY2. Researchers did not find any presence of MODY1. Four of the MODY3 mutations were novel that researchers could not place in any type and refer to them as un-typed cases. The conclusion is that some of the patients get MODY due to defects in the unknown genes but appear to have insulin resistance.

Causes of Autosomal Dominant And Recessive Mutations

Autosomal dominant mutations cause most forms of MODY meaning that these conditions can pass on to children even if it is just one parent who has or carries the disease gene. A parent with dominant mutations carries a gene with a 50 per cent chance of getting a child with monogenic diabetes. Some MODY cases also occur as a result of Autosomal recessive condition.

Autosomal dominant cases occur when a father or a mother are carriers MODY, and it puts the probability of passing the mutated gene to an offspring by 50%. In contrast, children can only get MODY by autosomal recessive if they inherit mutation from two parents. A child in such an instance has a 25 per cent chance of contracting monogenic diabetes.

Testing for recessive forms of monogenic diabetes can show whether parents or siblings are carriers without disease for latent genetic conditions that their children could inherit. It is possible to inherit mutations from a mother only (X linked mutations), but it is not widespread just like the occurrence of spontaneous mutations.

Genetic Testing of MODY

Doctors recommend genetic testing for MODY in the case of:

  • Diagnosis of diabetes within the first six months of age
  • Diagnosis of diabetes in children and the young adults especially those with a strong family history. These are the children who do not show regular features of diabetes type 1 or type 2 such as the presence of auto-antibodies, obesity, and the other relating metabolic features.
  • Stable mild fasting hyperglycemia especially if there is no presence of obesity

It is essential for those who think that a member of their family might be having a monogenic form of diabetes to consult a doctor. A doctor will offer advice on how to get the appropriate treatment and provide the right information about the existing type of diabetes such as stopping insulin.

Due to the high-risk chance of 50 per cent risk of passing MODY that a parent carries, it is important to discuss the risk to any children he or she plans to have and possible solutions. Genetic testing is available even for other members of the family of persons who think that they might have MODY.

MODY Testing Procedure

Testing MODY involves taking blood for pancreatic antibodies and urine or blood tested for C-peptide which is something that a personal doctor can do. Another method is to draw blood for genetic testing. The procedure starts with a doctor taking the blood from a patient but will send it to a specialist centre for testing together with the details of diagnosis and treatment.

Treatment and Management of MODY

Treatment of monogenic diabetes depends on a specific genetic mutation that causes the condition. Treatment with an oral diabetes medicine called sulfonylurea can help the body to release more insulin into the blood of people with certain forms of MODY.

Other people require insulin injections, yet others can manage the disease by lifestyle chance such as starting to eat a healthier diet and exercising. A diabetes specialist can work together with a patient’s physician to develop a beneficial plan for treating and managing diabetes based on the results of genetic testing.

MODY is a disease that a patient and doctor can manage and treat. Early detection makes a significant difference in the success of the treatment strategy. An accurate diagnosis is also essential in determining the correct pathway.

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